title: Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.
abstract: BACKGROUND
  Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease.
  
  
  OBJECTIVE
  To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study.
  
  
  METHODS
  Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial.
  
  
  RESULTS
  The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects.
  
  
  CONCLUSIONS
  TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. fleming@neurology.wisc.edu
authors.forename: J O
authors.initials: JO
authors.lastname: Fleming
authors.forename: A
authors.initials: A
authors.lastname: Isaak
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.forename: C C
authors.initials: CC
authors.lastname: Luzzio
authors.forename: M D
authors.initials: MD
authors.lastname: Carrithers
authors.forename: T D
authors.initials: TD
authors.lastname: Cook
authors.forename: A S
authors.initials: AS
authors.lastname: Field
authors.forename: J
authors.initials: J
authors.lastname: Boland
authors.forename: Z
authors.initials: Z
authors.lastname: Fabry
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D019936:Probiotics / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014258:Trichuris / Q000276:immunology; D015854:Up-Regulation; D014922:Wisconsin; D055815:Young Adult
chemical_list: D000909:Antibodies, Helminth; D015415:Biomarkers; C508609:IL10 protein, human; C508598:IL4 protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D002097:C-Reactive Protein